Serotonin:
Numerous studies have shown that serotonin (5-hydroxytryptamine, 5-HT)
generated by active platelets and neurons causes cerebral vasospasm in
patients with SAH (Heros & Zervas, 1983; Khey, Huard & Mahmoud, 2020).
SAH patients’ cerebrospinal fluid has been shown to cause considerable
constriction of isolated arteries, which may be prevented by the 5-HT
antagonist ketanserin. Additionally, tests of cerebral fluid
demonstrated elevated 5-HT levels during the acute, but not chronic,
spasm phase of SAH, while sustained exposure of arteries to 5-HT results
in desensitization (Szabò, Emilsson, Hardebo, Nystedt & Owman, 1992).
Additionally, it has been claimed that SAH may result in a boost of the
expression of 5-HT receptors (Ansar, Vikman, Nielsen & Edvinsson, 2007;
Hansen-Schwartz, 2004; Hansen-Schwartz, Hoel, Xu, Svendgaard &
Edvinsson, 2003) . Additionally, it was suggested that activating 5-HT1B
receptors activates the PLA2 (phospholipase A2) enzyme. The eicosanoid
20-HETE is then synthesized via PLA2 and works to amplify
vasoconstriction (Cambj-Sapunar, Yu, Harder & Roman, 2003) . Several
studies have shown that 5-HT receptors like 5-HT1B and 5-HT2A are
up-regulated after SAH, possibly via the MAPK-ERK1/2 pathway, hinting
that 5-HT receptors may be responsible for excessive vasoconstriction
(Ansar & Edvinsson, 2008; Ansar & Edvinsson, 2009; Ansar, Svendgaard
& Edvinsson, 2007) . More than a few studies have shown that inhibiting
5-HT or degenerating axons that contain 5HT do not relieve
experimentally induced vasospastic rats (Khey, Huard & Mahmoud, 2020).
The authors concluded that the disparity may be explained by the
cerebral arteries receiving insufficient 5-HT antagonist and 5-HT.